The proposed project extends the attempts to define biologically, genetically, diagnostically and therapeutically distinct subgroups of the schizophrenic-like illnesses. Recent studies have suggested that bimodal distributions of certain key biological findings occur in schizophrenic populations; unimodal distributions of similar parameters appear to occur in control populations. These biologic bimodalities (platelet MAO, growth hormone response to apomorphine, membrane ion counterflow deficiencis and, perhaps, stimulated adenylate cyclase activity in platelet and WBC) provide the basis for investigations of different gentic, diangnostic and treatment respone groups. More specifically, each of 40 additional patients diagnosed as schizophrenia or schizoaffective disorder will undergo biologic testing on the parameters noted above, will be further explored diagnostcally with he physostigmine challenge and will then undergo a two week therapeutic trial with lithium. Lithium responders will be studied dring subsequent litium maintenance for reduction of morbidity. First degree relatives of all patients will be studied for evidence of affective or schizophrenic histories. Data analysis will determine whether a subgroup of the schizophrenic population can be defined which manifests characteristic abnormalities by biological testing, which have family history of affective-like disorders, which can be diagnosed clinically and which respond to lithium. Such a group would be contrasted to other group(s) of schizophrenic-like illness which show differing biologic patterns, whiih may have evidence of schnizophrenic illness in family members, which can be distinguised by specific diagnostic parameters and which fail to respond to lithium. The delineation by multivariate analysis of such subgroups of he schizophrenic population is the goal of the proposed work.